Friday, July 15, 2011

Tysabri-related PML Death Cases Total 29 in July 2011

Five more patients who had developed PML after using Tysabri have died.  Biogen Idec reports that there are 12 more cases of the brain infection, progressive multifocal leukoencephalopathy (PML).  Total cases of PML equal 145 and total deaths equal 29 to date.

Since I was traveling, I missed the announcement of new cases in June and can not find the information published for last month.  However, based on information in this announcement (seen below), we can deduce how many cases there were in June 2011.

Here is an updated table including total of PML cases reported to date:

Here is a chart showing the rate of increase of reported cases of PML and deaths:

The following is the announcement as published by Dow Jones and republished online by the Multiple Sclerosis Resource Centre (MSRC):

Biogen Idec Inc. reported 12 more cases of a rare brain infection occurring in multiple-sclerosis patients taking the drug Tysabri, sold with Elan Corp, bringing the affected patients to 145 as of July 5.

The Weston, Mass., biotech company said there was five more deaths among those patients, bringing total deaths to 29, and provided updated data on its effort to develop a risk-assessment test for the infection. The incidence of the infection -- progressive multifocal leukoencephalopathy, or PML -- is updated monthly and is closely watched.

The drug is considered to be highly effective, but it is mostly reserved for patients that stop responding to other MS drugs or have an aggressive case of the debilitating disease.
Biogen is developing a blood test for antibodies to a specific virus, JC virus, something that may better determine the chances of patients contracting PML.

Many people carry JC virus and it causes no harm, but some biologic drugs that modulate the immune system, including Tysabri, appear to promote activation of JC virus in some patients, leading to PML.

Biogen reported that one patient diagnosed with PML among the latest data actually tested negative for the JCV antibody at the time of diagnosis. The company said the outcome was likely because the test was given after use of plasma-exchange therapy, a process that removes large molecules from the body's blood that accelerates removal of Tysabri and theoretically improving the immune response to PML infection.

The company doesn't know why the patient's physician used the test in that way, a spokeswoman said.

The process of testing newly diagnosed patients -- who by definition should be positive with the JCV antibodies -- is a way of testing the effectiveness of the diagnostic tool. Of those tested, 46 out of 47 were positive at diagnosis.

Among patients with JCV antibody status data from prior to diagnosis with PML, 30 patients that developed the infection previously had the JCV antibodies.

Regulators monitor cases of PML as they occur and have repeatedly said that the benefits of the medicine outweigh the risks. Tysabri was withdrawn from the market in 2005 and relaunched in 2006 -- amid advocacy from patients and physicians that stressed it effectiveness -- with a strict access plan that regularly monitors patients.

The overall global PML rate is now at 1.62 per 1,000 patients. Of the total PML cases, 57 were in the U.S., 81 were in the European Union and seven were in other areas.
The company believes that the best way to assess the pool of PML data shows all patients over a fixed duration range of treatment.

According to that method, the rate is about 1.94 cases per 1,000 patients on the drug for between two and three years. The incidence is about 0.54 case per 1,000 patients in those using it for one to two years, and it is essentially nonexistent in patients using it for less than a year.

For patients on the drug for three to four years, the rate drops to 1.34 patients per 1,000, but Biogen doesn't believe there is enough data to conclude that incidence of the infection drops after a certain amount of time.

Looked at another way, the rate is 2.41 cases per 1,000 patients on the drug for a year or longer, rising to 3.03 per 1,000 for those on the drug for two years or longer, and dropping to 1.85 for more than three years.

Source: Dow Jones Newswires Copyright (c) 2011 Dow Jones & Company, Inc. (15/07/11)


  1. I think the column on the right is an interesting one as it suggests that PML as a % is fairly stable at roughly 20%. That paints quite a different image than the sharply upward sloping bar curve of actual incidents.

  2. Additional comment: that 20% is alarming all on its own since it's roughly 1/5 of those who come down with PML. An interesting graph would be the progression over time of the incidence of PML in all patients, and whether that is also moving sharply upward. These numbers can obviously be read and anlyzed in so many different ways.


  3. Judy,
    I am intrigued with the ~20% death rate of PML patients which translates into an 80% survival rate (although we don't know the condition of the surviving patients).

    I'm a number cruncher and there would be many ways to analyze the data as a moving target. If I had complete information for other variables, it would be nice to took at them.

    But without the info, it's hard to d our own analysis. Just look at the numbers reported here which seem to be starkly contradictory:

    "...the rate is about 1.94 case per 1,000 patients on the drug between two and three years."


    "...the rate [rises to] 3.03 cases per 1,000 patients on the drug for two years or longer..."

  4. I've been a Tysabri patient for three years. One Monday I'll have my 40th infusion and begin year 4. I've tested negative for JCV (and I hope it stays that way).

    I was Dx with MS in early 2005. I took copaxone for almost three years. When I decided I needed to switch because I couldn't keep giving myself shots every day, I had an MRI, and we saw the number of lesions had increased from 2 to 10 in one year.

    I'm very happy on Tysabri, but I'm also wary of PML. Thanks for continuing to share this information.

  5. Hi Lisa

    Many thanks for the update. My name is Declan Walsh, and my wife, Natalie, is unfortunately, one of those statistics, having contracted Tysabri related PML in November 2009.
    I have set up a trust and information portal for all those that may be affected by this and would be interested in keeping in touch. Please see (the site is offline getting some work done for a few days) but there is also a very active Facebook page (search for the Deferno Trust).
    As a number cruncher myself, I can get very agrreived at the manner in which the stats can be just rolled out.
    As a side, there is a conference on drug related PML in London at the EMA offices, on 25 & 26 July.
    Thanks for your post and hopefully we can keep in touch